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Genome-wide gene expression profiling in children with non-obese obstructive sleep apnea
Abdelnaby Khalyfa1, Oscar Sans Capdevila, Mohamed O Buazza
1Kosair Children's Hospital Research Institute, Department of Pediatrics, University of Louisville, 570 South Preston Street, Suite 204, Louisville, KY 40202, USA.
Insights
Pediatric obstructive sleep apnea (OSA) alters gene expression in white blood cells, indicating potential inflammatory pathways. This finding in children with OSA highlights the disorder's complex genetic and environmental influences.
Area of Science:
- Genomics
- Molecular Biology
- Pediatric Medicine
Background:
- Obstructive sleep apnea (OSA) is a common, multifactorial disorder with potential genetic and environmental links.
- Untreated OSA can lead to serious cardiovascular and neurocognitive issues.
- The study investigated gene expression changes in children with OSA.
Purpose of the Study:
- To identify differences in gene expression in circulating leukocytes of children with OSA compared to healthy controls.
- To explore the biological pathways associated with altered gene expression in pediatric OSA.
Main Methods:
- Oligonucleotide-based microarray technology was used to analyze gene expression in 40 children (20 with OSA, 20 controls).
- RNA was extracted from blood samples, labeled, and hybridized to microarrays.
- Quantitative RT-PCR was employed for validation of microarray findings.
Main Results:
- Out of 44,000 transcripts, 1217 were differentially expressed in children with OSA (p<0.05).
- 68 transcripts met high-stringency criteria for differential expression.
- Analysis revealed significant involvement of inflammatory pathways.
Conclusions:
- Gene expression in peripheral leukocytes is altered in pediatric OSA.
- Large-scale genomic studies can offer insights into OSA's mechanisms, including adaptation and end-organ injury in children.
Background:
Obstructive sleep apnea (OSA) is a multi-factorial and highly prevalent disorder in which both genetic and environmental factors may be involved. If left untreated, OSA may lead to significant cardiovascular and neurocognitive and behavioral morbidities. We hypothesized that pediatric OSA would lead to altered gene expression in circulating leukocytes.
Methods And Results:
Oligonucleotide-based microarray technology was used to identify mRNAs that may be differentially regulated in non-obese children with polysomnographically-established OSA compared to matched control children. Total morning blood RNA from 40 children (20 OSA and 20 controls) was extracted, labeled, and hybridized onto independent oligonucleotide-based microarrays. Of the 44,000 transcripts, 1217 transcripts were differentially expressed in OSA (p-value <0.05), with 68 transcripts (38 RefSeq accession numbers, 30 ESTs) fulfilling high stringency criteria. False Discovery rate (FDR) was used to determine the significance-difference of OSA vs. normal samples. Microarray data were further validated using quantitative RT-PCR techniques. Biological pathways pertinent to the differentially expressed genes were explored and revealed prominent involvement of inflammatory pathways.
Conclusions:
RNA derived from peripheral leukocytes confirms the presence of altered expression of functionally relevant gene clusters in pediatric OSA. Large-scale genomic approaches may provide further insights into adaptive and end-organ injury related mechanisms in the context of OSA in children.
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